Mortality and cancer incidence in carriers of constitutional t(11;22)(q23;q11) translocations: A prospective study

Abstract

The constitutional t(11;22)(q23;q11) translocation is the only recurrent non‐Robertsonian translocation known in humans. Carriers are phenotypically normal and are usually referred for cytogenetic testing because of multiple miscarriages, infertility, or having aneuploidy in offspring. A breast cancer predisposition has been suggested, but previous studies have been small and had methodological shortcomings. We therefore conducted a long‐term prospective study of cancer and mortality risk in carriers. We followed 65 male and 101 female carriers of t(11;22)(q23;q11) diagnosed in cytogenetic laboratories in Britain during 1976–2005 for cancer and deaths for an average of 21.4 years per subject. Standardised mortality (SMR) and incidence (SIR) ratios were calculated comparing the numbers of observed events with those expected from national age‐, sex‐, country‐ and calendar‐period‐specific population rates. Cancer incidence was borderline significantly raised for cancer overall (SIR = 1.56, 95% CI: 0.98–2.36, n = 22), and significantly raised for invasive breast cancer (SIR = 2.74, 95% CI: 1.18–5.40, n = 8) and in situ breast cancer (SIR = 13.0, 95% CI: 3.55–33.4, n = 4). Breast cancer risks were particularly increased at ages <50 (SIR = 4.37, 95% CI: 1.42–10.2 for invasive, SIR = 22.8, 95% CI: 2.76–82.5 for in situ). Mortality was borderline significantly raised for breast cancer (SMR = 4.82, 95% CI: 0.99–14.1) but not significantly raised for other cancers or causes. Individuals diagnosed with t(11;22)(q23;q11) appear to be at several‐fold increased breast cancer risk, with the greatest risks at premenopausal ages. Further research is required to understand the genetic mechanism involving 11q23 and 22q11 and there may be a need for enhanced breast cancer surveillance among female carriers.

Palindromes in DNA—A Risk for Genome Stability and Implications in Cancer

“…Reciprocal translocation with breakpoints in these palindromic sequences produces balanced carriers which are, for the most part, healthy. They do have an increased risk of developing breast cancer [ 97 ], as well as infertility issues and recurrent pregnancy losses. However, if the small derivative of chromosome 22 produced by translocation is passed on alongside the normal chromosome set, the zygote is viable.…”

Cruciform DNA in mouse growing oocytes: Its dynamics and its relationship with DNA transcription

“…In these cruciform DNA-mediated translocations, t(11;22)(q23;q11) has the most higher prevalence in human and got most attentions and investigations [ 3 ]. Although t(11;22)(q23;q11) carriers are generally phenotypically normal, their fertility is lower comparing to normal individuals as chromosomal translocations induce miscarriage during pregnancy, and they also have higher risks of breast cancer [ 6 ]. In addition, offspring of t(11;22)(q23;q11) carriers might inherit unbalanced form of chromosomal translocation which could induce the Emanuel syndrome [ 7 ].…”